At the time of an initial Xindi attack on Earth, later that same year, the ship was still under construction (and unnamed), but was scheduled to be completed and launched by mid-2154. A tour of Columbia was taken by Captain Archer and AdmiralForrest shortly before Enterprise began a mission to find the Xindi, in the Delphic Expanse, and prevent them from destroying Earth. (ENT: "The Expanse") At one point during that mission, in early 2154, LieutenantMalcolm Reed initially suggested that an NX-class starship encountered by Enterprise might be Columbia, only for Reed and the rest of Enterprise's senior staff to then discover that the ship in question wasn't Columbia but was actually an alternate version of Enterprise. ("E²")

In the original story of "E²" pitched by writer/producer Mike Sussman, the NX-class starship encountered by Enterprise in the Delphic Expanse was indeed the Columbia, having used Xindi subspace vortex technology to journey from Earth to the Delphic Expanse in order to help Enterprise in its mission. Due to an incompatibility in respective technologies, Columbia would have arrived in the Expanse more than a century in the past and been marooned there. Consequently, a one-hundred year old Columbia, operated by the descendants of its original crew, would have been encountered by Archer and his crew during the course of the story. When Sussman was asked to revise the narrative, though, Columbia was written out of the plot. (Information from Mike Sussman)

Several months before launch, Columbia's commanding officer, CaptainErika Hernandez, invited Captain Archer aboard to view construction efforts and to enlist his aid in crew selection. Archer suggested she consider a MACO as tactical officer, and also suggested modifications to the ship, including a larger arsenal with which to defend the ship. Captain Hernandez rejected the idea of a MACO on the bridge, while Captain Archer was discomforted by her somewhat positive attitude towards exploration and inexperience as a military commander when compared to his own experiences. (ENT: "Home")

Columbia was still understaffed prior to its launch. Captain Hernandez had twice offered CommanderCharles Tucker III, chief engineer aboard Enterprise, a position aboard Columbia, which he had rejected. Following the Babel Crisis, however, Tucker finally accepted Hernandez's offer and requested a transfer to Columbia to help fulfill that ship's need for experienced officers. (ENT: "The Aenar") One of the first changes Captain Hernandez advised Tucker to make was to switch his uniform so its mission patch represented Columbia, not Enterprise. (ENT: "Affliction")

Tucker's hard driving work ethic prompted two crew members to unsuccessfully request transfer off the engineering team. Captain Hernandez refused these transfer requests stating that the engineering team was already short staffed. While Tucker said he may have "knocked some heads together" the ship would soon be warping out of dry dock. Commander Tucker was successful in repairing Columbia's engine problems, and the vessel was able to be launched on November 30th, 2154. (ENT: "Affliction", "Bound")

Upon its launch in "Affliction", Columbia was scripted to be shown with an upwards-looking "majestic angle." In the final version of the ship's launch, however, the ship is shown with a downwards-looking angle.

Soon after the launch of Columbia, the ship was called into service to assist Enterprise after that vessel had been sabotaged by Klingon forces. The two craft engaged in hazardous close-quarter maneuvering at warp 5.2, allowing Tucker to be transferred over to fix the problem. Columbia also assisted in recovering DoctorPhlox from Qu'Vat Colony, engaging in battle with several Klingon vessels. (ENT: "Divergence")

Following the resolution of that crisis, Tucker transferred back to Enterprise and resumed his duties. (ENT: "Bound")

Columbia also featured ventral and dorsal photonic torpedo launchers as well as pulsed phase cannons (a relatively new technology, at that time). Other improvements included improved computer interface technology and a modified bridge interior, utilizing stations that were tied directly into the primary EPS junction. (ENT: "Home") Compared to the bridge of Enterprise, Columbia's bridge featured several structural additions, such as four vertical bars of light behind the captain's chair and a computer monitor mounted on vertical metal tubes next to the helm. Computer consoles aboard Columbia were also different from those aboard Enterprise, in that they included a red, yellow and green color scheme instead of red, yellow and blue. Between Captain Archer's visit aboard the ship in 2154 and November of that year, the captain's chair as well as several cosmetic details on Columbia's bridge changed, mirroring alterations aboard Enterprise. (ENT: "Home", "Affliction")

The upgrades on Columbia's bridge are installed sometime between the setting of "Home" and that of "Affliction", whereas the changes to Enterprise take place between "Home" and "Borderland".

Spaceframe and major structural elements of the NX-02, however, were generally identical to that of her predecessor. (ENT: "Affliction")

The bridge of the NX-02 was represented with a redress of the set used as the NX-01's bridge. The structural additions to the Columbia bridge were set pieces that had previously been used in the episode "E²", on the bridge of the "future" Enterprise of that installment. The aforementioned computer monitor on vertical metal tubes reappeared aboard another "future" Enterprise, in "These Are the Voyages...". Columbia's engine room was also a redress of that seen aboard Enterprise, with only minor details added to the bulkheads.

The color scheme of red, yellow and green for the computer displays matches that seen on computer consoles in Star Trek: The Original Series, an homage to that series and a suggestion of advancement in technology. This was, however, also seen on a "future" Enterprise, when it was used in "Twilight".

While Hernandez's crew was never fleshed out in an episode, judging from those present on the bridge, it is safe to conclude that no Vulcans were included in the senior staff.

Seth MacFarlane (also known as the creator of FOX's Family Guy) appears aboard Columbia as engineer Rivers. He had previously appeared as the same engineer aboard Enterprise in "The Forgotten", suggesting that his character transferred between the two vessels.

In the final draft script of ENT: "Desert Crossing" but not in the final version of that episode, Commander Tucker reckoned, "Won't be too long before the next warp five ship comes along, sets a new record..."

At a point when the ship was not yet named, Star Trekfan Anthony Davis of Brentwood, Tennessee, suggested to Rick Berman that the craft be named Columbia, in honor of the crew of a space shuttle which bore the same name. (Star Trek: Communicator issue 149, p. 14) The selection of this starship's name, mirroring the fact that the second space shuttle was named Columbia, followed on from the ship's NX-class predecessor having been named after space shuttle prototypeEnterprise. The starship Columbia was given its name, by the creators of Star Trek: Enterprise, as a tribute to the STS-107 crew of the Space ShuttleColumbia. ("Before Her Time: Decommissioning Enterprise, Part Two: Memorable Voyages", ENT Season 4 Blu-ray special features; Star Trek Encyclopedia (4th ed., vol. 1, p. 154)) This shuttle and its crew were lost when the craft disintegrated, while attempting re-entry into Earth's atmosphere on 1 February2003. Like Star Trek: Enterprise's Columbia assignment patch, the real STS-107 mission insignia featured seven background stars. Stars often represent the number of crew members on NASA mission insignia.

Columbia was first mentioned in "Fortunate Son" and seen under construction in second season finale "The Expanse". However, neither of those appearances referred to the ship by its name.

In an ultimately excised scene extension from the final draft script of "Home", Archer asked Hernandez how soon Columbia's launch would be and Hernandez replied, "A few months... I hope. Forrest pushed back the launch date twice... we’ve had trouble with the intercooler matrix." After Archer suggested he might be able to help, Hernandez offered him a guided tour of the ship.

There was more than one link between Star Trek: Enterprise's Columbia and NASA. "NASA heard that [...] the show was naming the second [NX-class starship] Columbia," recalled Garfield Reeves-Stevens, "and we got feelers that the astronauts currently onboard space station wanted to record a little 'Godspeed to Columbia,' and, uh, just, it'd be a little fifteen-second thing that we could throw at the beginning of the episode." However, the supportive message was never recorded, because it was too much trouble to go through all the studio approval proceedings and because the corporation Paramount lacked enthusiasm for the idea, which clued the ENT writing staff into the fact that the series was about to be cancelled. ("Before Her Time: Decommissioning Enterprise, Part Two: Memorable Voyages", ENT Season 4 Blu-ray special features)

The novel series Star Trek: Destiny is based upon the events surrounding the mysterious destruction of Columbia and the ship's final resting place. In the same novels, Columbia also featured heavily in the creation of the Borg Collective.

In the reference book Federation: The First 150 Years, the Columbia is mentioned as being destroyed during the Romulan War. The ship was trying to defend Starbase One, as well as buy time for the third Warp 5 starship, NX-03 Challenger to send a message to Starfleet Command. CaptainErika Hernandez was killed along with all hands.